Angiotensin II exerts glucose-dependent effects on K^sub v^ currents in mouse pancreatic [beta]-cells via angiotensin II type 2 receptors

Hyperglycemia-associated glucotoxicity induces β-cell apoptosis but the underlying mechanisms are unknown. Interestingly, prolonged exposure to high glucose upregulates the expression and function of the renin-angiotensin system (RAS). We hypothesize that the voltage-gated outward potassium (K...) c...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2010-02, Vol.298 (2), p.C313
Main Authors: Chu, Kwan Yi, Cheng, Qianni, Chen, Chen, Au, Lai Shan, Seto, Sai Wang, Tuo, Ya, Motin, Leonid, Kwan, Yiu Wa, Leung, Po Sing
Format: Article
Language:English
Subjects:
Apoptosis
Cells
Glucose
Hyperglycemia
Pancreas
Potassium
Rodents
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Summary:Hyperglycemia-associated glucotoxicity induces β-cell apoptosis but the underlying mechanisms are unknown. Interestingly, prolonged exposure to high glucose upregulates the expression and function of the renin-angiotensin system (RAS). We hypothesize that the voltage-gated outward potassium (K...) current, which governs β-cell membrane potential and insulin secretion, has a role in glucotoxicity. In this study, we investigated the effects of prolonged exposure to high glucose on mouse pancreatic β-cells and concurrent effects on the RAS by examining changes in expression of angiotensin II (ANG II) receptors and changes in the expression and activity of K... channels. β-Cells were incubated in high glucose medium for 1-7 days and then were examined with electrophysiological and molecular biology techniques. Prolonged exposure to high glucose produced a marked increase in β-cell primary K... channel subunit, K...2.1, expression and K... current amplitude. Enhanced expression of ANG II type 1 receptor (AT...R) was also observed under high glucose conditions, whereas blockade of AT...R by losartan did not alter K... channel expression. External application of ANG II reduced K... current amplitude under normal, but not high, glucose conditions. The effect of ANG II on K... channel gating was abolished by ANG II type 2 receptor (AT...R) antagonism. These data suggest that hyperglycemia alters β-cell function through modification of the K... channel which may be associated with the RAS. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0363-6143
1522-1563